There is strong evidence that the medication apixaban (Eliquis) is preferable to rivaroxaban (Xarelto) for stroke prevention in patients with atrial fibrillation (AF), with both reduced rates of severe bleeding complications as well as strokes, according to study published Dec. 21 in JAMA.
An estimated 3 million to 6 million persons in the United States have AF. Patients with AF are at five-fold risk of forming clots that can migrate to the brain and cause dangerous strokes. These can be prevented by chronic administration of blood-thinning drugs (anticoagulants) such as apixaban or rivaroxaban, but these medications come with their own risks, including an increased risk of excessive bleeding.
Investigators at Vanderbilt University Medical Center (VUMC) conducted a retrospective study using data for more than 580,000 Medicare beneficiaries age 65 and older who were treated with either apixaban or rivaroxaban, two of the most commonly prescribed medications for AF, during a six-year period. Investigators tracked occurrences of both major ischemic (stroke and systemic embolism) events and major bleeding events (including intracerebral hemorrhage or other intracranial bleeding and fatal extracranial bleeding). Individuals were followed for up to four years, beginning the day after filling the initial oral anticoagulant prescription.
They found that the rivaroxaban group had increased risk for both major ischemic events (8.6 versus 7.6 per 1,000 person years) and hemorrhagic events (7.5 versus 5.9 per 1,000 person years), including fatal extracranial bleeding (1.4 versus 1.0 per 1,000 person years). Patients receiving rivaroxaban also had increased risk of nonfatal extracranial bleeding (39.7 versus 18.5 per 1,000 person years), fatal ischemic/hemorrhagic events (4.5 versus 3.3 per 1,000 person years) and total mortality (44.2 versus 41.0 per 1,000 person years). The risk of a stroke or systemic embolism was increased for rivaroxaban in both those receiving a reduced dose and the standard dose.
“Our study offers compelling evidence that apixaban is preferable to rivaroxaban for stoke prevention in patients with atrial fibrillation, with both reduced rates of severe bleeding complications as well as better efficacy for reducing stroke occurrence,” said the study’s principal investigator Wayne Ray, PhD, a professor of Health Policy at VUMC. “The findings were not entirely surprising.
“Although rivaroxaban and apixaban have comparable half-lives, rivaroxaban is taken once daily vs twice for apixaban. This leads to greater fluctuation in plasma concentrations — higher highs and lower lows. There has been concern that bleeding risk might be increased during periods of elevated concentrations and efficacy reduced when concentrations were reduced.”
While there have been previous retrospective studies that have compared the relative effectiveness in treating AF of the two medications, this study examined a significantly larger population than previous studies and focused entirely on individuals 65 or older who are at the highest risk of AF. The study also included patients who were treated with reduced doses of the medications, showing risk is elevated at both reduced and standard dosage levels. The study also provided an integrated measure of the benefits and harms of anticoagulation for those with AF.
“We hope that patients with atrial fibrillation and their providers will strongly consider these data when selecting an oral anticoagulant for stroke prevention, as our findings indicate that apixaban should generally be preferred to rivaroxaban,” Ray said.
In addition to Ray, study authors include Cecilia Chung, MD, MPH; Michael Stein, MBChB; Walter Smalley, MD, MPH; Eli Zimmerman, MD; William Dupont, PhD; Adriana Hung, MD, MPH; James Daugherty, MS; Alyson Dickson, MA; and Katherine Murray, MD.
The study was supported by a grant from the National Heart, Lung, and Blood Institute (HL151523).
